| Literature DB >> 25754822 |
Hyun Kyoung Lee1, Lesley S Chaboub2, Wenyi Zhu3, Daniel Zollinger4, Matthew N Rasband4, Stephen P J Fancy5, Benjamin Deneen6.
Abstract
Wnt signaling plays an essential role in developmental and regenerative myelination of the CNS; however, contributions of proximal regulators of the Wnt receptor complex to these processes remain undefined. To identify components of the Wnt pathway that regulate these processes, we applied a multifaceted discovery platform and found that Daam2-PIP5K comprise a novel pathway regulating Wnt signaling and myelination. Using dorsal patterning of the chick spinal cord we found that Daam2 promotes Wnt signaling and receptor complex formation through PIP5K-PIP2. Analysis of Daam2 function in oligodendrocytes (OLs) revealed that it suppresses OL differentiation during development, after white matter injury (WMI), and is expressed in human white matter lesions. These findings suggest a pharmacological strategy to inhibit Daam2-PIP5K function, application of which stimulates remyelination after WMI. Put together, our studies integrate information from multiple systems to identify a novel regulatory pathway for Wnt signaling and potential therapeutic target for WMI.Entities:
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Year: 2015 PMID： 25754822 PMCID： PMC4402944 DOI： 10.1016/j.neuron.2015.02.024
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173